Drugs and the Eye Part 1 & 2 Flashcards
What are the different types of drugs used by optometrists?
■Diagnostic drugs e.g. mydriatics, cycloplegics, topical anaesthetics
■Lubricants e.g. Hypromellose, Sodium Hyaluronate
■Anti-infectives e.g. Fusidic acid, Chloramphenicol
■Anti-allergy (anti-histamines and mast cell stabilizers)
Specialist Therapeutic Prescribers
■Corticosteroids
■Anti-glaucoma
What does NSAID stand for?
Non steroidal anti-inflammatory drug
What drugs are examples of Non-Steroidal anti-inflammatory drugs?
Aspirin and Ibuprofen
What are the different routes of administering drugs?
Topical
Intra-ocular
Systemic
What does systemic refer to?
in regards to drugs it refers to it circulating the whole body
True or false- drugs can be both diagnostic and therapeutic
True
What is a peri-optive drug?
A drug typically used immediately before and after surgery
( from the latin of peri to mean around)
What is bioavailability?
Bioavailability basically refers to how much of the drug reaches its desired target.
How can we arrange factors affecting topical drug delivery to the eye?
(really bad question just here to structure the lesson)
- pre-corneal
- corneal
- what happens as the drug enters the eye
If eye drops are applied to an eye with a high tear turn over what does this mean for the penetration of the drug inside the eye?
Essentially an eye drop would be applied to the surface of the eye - our tears are always being replenished ( tear turn over) - a high rate of replenishing of these tears means a greater amount of tear drainage and so alot of the drug is being drained away before it can penetrate into the cornea.
True or False- the amount of drug from an eye drop that penetrates the cornea is greater than that which is drained away into the nasolacrimal sac
False - the amount of drug that gets drained via the nasolacrimal gland actually exceeds the amount that penetrates into the cornea as a single drop from a conventional dropper bottle exceeds the capacity of the conjunctival sac.
Does a bigger drop equal more corneal penetration?
As a single drop from a conventional doper bottle exceeds the capacity of the conjunctival sac a bigger drop does not equal more corneal penetration but rather an increased risk of systemic toxicity.
How can large drops of ocular drugs cause systemic toxicity?
The capacity of the conjunctival sac is smaller than that of a conventional drop dose of a drug and so it gets drained away into the nasolacrimal sac where it can cross into the nasopharynx ansd thus ios able to cross the mucosa and enter general ciurculation.
True or False - higher drop sizes are associated with higher rates of drainage.
True
How is bioavailability affected by higher rates of drainage?
beyond a certain drop size it plateaus
What is a contraindication for the prescribing of beta blockers to reduce pressure in the eyes of patients with glaucoma?
Beta blockers in general criculation also cause constriction of the airways and so are not prescribed to asthma pxs or pxs with chronic obstructed airways.
What difficulties does the structure of the cornea cause for corneal penetration of drugs?
The epithelium and endothelium are lipid based and so lipid based drugs can penetrate rapidly.
However, the stroma of the cornea is hydrophilic and thus slows down the passage of lipid based drugs and only allows hydrophilic drugs to pass through rapidly.
What kind of drugs are needed for optimal corneal penetration?
Drugs that have a combination of hydrophilic and hydophobic porperties. These usually tend to be weak acids and bases that sort of start more stable then get ionised and so let through the stroma and then become more stable again.
When a drug is ionised is it hydrophobic or hydrophilic?
Hydrophilic
What is ocular morbidity?
The condition of suffering from an ocular disease
Can ocular morbidity affect drug penetration?
yes
True or False - Some drugs aren’t intended to penetrate inside the eye
True - e.g. topical anaesthetics
Following corneal penetration where does the drug end up?
Distributed in the aqueous humour
What is the intended target of tropicamide?
Muscarinic receptors within the sphincter pupillae of iris
What is the target of cyclopentolate?
Muscarinic receptors in the ciliary body
How does aqeous humour drainage affect bioavailaibility of drugs?
Aqueous humor is in a constate state of being renewed/replaced (as well as drained) and so some of the drug that has passed through the cornea is lost away via drainage, reducing bioavailability.
Does melanin binding reduce bioavailability?
Technically no - because melanin binding isn’t permanent it just delays the drug from getting to where it is suppose to.
How does melanin binding affect time it takes for drug to ‘kick’ in?
Melanin binds to certain drugs like tropicamide delaying transit thus more time is reqired for the drug to cause an effect - to counteract this we use a higher concentration
What are types of different intra-ocular targets?
Enzymes and receptors
What effect upon what target receptor does phenylephrine have?
Phenylephrine acts on the sympatehtic nervous system on adrenergic receptors as an agonist on the dilator pupillae
True or False- there are no drug metabolising enzymes in the eye
False - there are many drug metabolising enzymes in the eye - many are located in the cornea.
True or False- some drugs are broken down in transit by ocular tissues durring corneal penetration
True
What is a pro-drug?
A drug that in its parent form is inactive but actually becomes activated via an enzyme
What is a good example of an ocular pro-drug?
Latanoprost - it is metabolised by enzymes (specifically estrases) on transit through the cornea.
What is latanoprost used to treat?
Glaucoma - it is an anti-glaucoma drug
Following corneal penetration and distribution in the eye how are drugs gotten rid of (excreeted)?
They are eliminated from the aqueous humour by a combination of aqueous turnover and absorption into the tissues of the anterior uvea
True or False- drug binding to melanin is a form of drug excreetion
False - its just a hinderance in drug distribution as eventually the drug is released from its binding with melanin
True or False - drug binding can occur to the iris and ciliary body
True which again can affect bioavailability - and predispose someone to toxicity
What factors affect systemic drug delivery to the eye?
■Blood-ocular barriers
■Plasma protein binding
■Active transport
How does a blood-ocular/blood-aqeous barrier affect the delivery of a systemic drug to the eye?
■The blood-aqueous barrier limits the free access of systemic drugs to the anterior chamber this is through the use of tight junctions and low permeability.
■The main components of the BAB are the “tight” ciliary epithelium and low permeability of iris blood vessels (stoping thr drugs getting through).
True or False- tight junctions of the blood-aqueous barrier reduce bioavalability
True
True or False- there is such thing as a blood-retinal barrier
True
Similarly to the blood-aqueous barrier what is the blood retinal barrier formed by consist of and how does this affect bioavailability?
■The blood-retinal barrier is formed by tight junctions between capillary endothelial cells and retinal pigment epithelial cells
■Limits the passage of all but the smallest lipid-soluble molecules
Why is the blood retinal barrier not as much of a cause for concern?
Several drug transporters have been idnetified at the blood retinal barrier
What do we value more ocular comfort or drug stability?
Drug stability
Are insoluble drugs maintained in solutions or suspensions?
Suspensions
True or False - Some drugs require specific pHs to retain solubility
True
Once a multi-dose drug bottle is opened what is the drug susceptible to?
Once a multi-dose bottle is opened the drug is subject to oxidative damage and bacterial contamination
Why are multi-dose drug bottles used?
They are more convenient from a cost perspective + less plastic waste
What is the problem with drugs that exist as suspensions?
Eventually overtime particles settle at the bottom and so you have to make sure you shake well before use.
What drug sterilisation methods are there?
■Heat
■Sterile filtration
and gamma radiation
True or False- all intra-ocular drugs are preservative free
True - key word being INTRA-ocular
What is the purpose of preservatives?
preservatives prevent unwanted microbial growth
Why must any solution entering the eye (i.e. INTRA-ocular drugs) be preservative free?
preservatives are potentially toxic to ocular tissues therefore any solution entering the eye must be preservative free
What is the most commonly used ocular preservative?
BAK (Benzalkonium chloride)
What are excipients?
Inactive ingredients used in ophthalmic formulations to ensure drug stability and sterility.
What are different types of excipients?
■Preservatives
■Buffers
■Antioxidants
■Viscous agents
■Tonicity-adjusting agents
■pH adjusting agents
Why are buffers used in opthalmic formulations?
Buffers maintain a constant pH which is soemtimes needed by specific drugs to work at their optimal and thus increase bioavailability
Why are viscous agents used in ophthalmic formulations?
Visocus agents increase viscosity - increased viscosity means increased contact time on the cornea (as essentially the drug isn’t being washed away as easily), thus increasing absorbption.
What is chloramphenicol?
It is a common ocular antibiotic
What is “water for injection” which is a commonly listed ingrediant in ophthalmic drugs?
It is just another name for sterile water
Why do we care about adding anti-oxidants to ocular drugs?
As drugs can be destabilised by oxidative breakdown ( basically the drug reacting with air can ruin the drug).
What do anti-oxidants do?
■Prevent or delay deterioration of the drug by oxygen in the air
What is an example of an antioxidant?
■EDTA
What do preservatives do?
Destroy or inhibit the growth of micro-organsims
What’s the benefit of these newer formulations of preservatives?
They are tending to be less toxic
Why is BAK such a widely used preservative?
■Effective against a wide range of GM +ve and GM -ve organsisms
■Concentration; 0.004-0.02% - basically it only needs to be used in a low concentration
■Excellent chemical stability
What are cons of using BAK as a preservative?
It is unsuitable for contact lens wearers as it binds to hydrogel.
It also affects corneal penetration
What are some common side effects of preservatives?
Stinging or burning
Dry eye sensation
excessive tearing
As well as pH why do we also sometimes adjust osmolarity of an ocular drug?
For comfort so that solution is isotonic to tears
sometimes solutions also need to be at particular osmolarities to maximise shelf life.
What are examples of osmolarity adjusting agents?
■Mannitol
■NaCl
What are the names of some newer ophthalmic drugs?
polyquad as its safe to use in contact lens solutions
purite
What are examples of ophthalmic buffers?
■Boric acid
■Potassium bicarbonate
What are examples of viscous agents in ophthalmic drugs?
■Methyl cellulose
■Poly vinyl alcohol
■Carbomers
What are examples of pH adjusting agents in ophthalmic drugs?
■Hydrochloric acid
■Sodium hydroxide
